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1.
Clin Mol Hepatol ; 23(4): 331-339, 2017 12.
Article in English | MEDLINE | ID: mdl-28946736

ABSTRACT

BACKGROUND/AIMS: Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are limited. This study evaluated the efficacy and safety of entecavir (ETV) and lamivudine (LAM) over 240 weeks. METHODS: Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA<300 copies/mL) at week 24. Secondary objectives included alanine aminotransferase (ALT) normalization and emergence of ETV resistance (week 96), VR and log reduction in HBV DNA levels (week 240), and safety evaluation. RESULTS: In total, 120 patients (>16 years old) were included (ETV, n=56; LAM, n=64). Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (92.9% vs. 67.2%, P=0.0006), week 96 (94.6% vs. 48.4%, P<0.0001), and week 240 (95.0% vs. 47.6%, P<0.0001). At week 96, ALT normalization was observed in 87.5% and 51.6% of ETV and LAM patients, respectively (P<0.0001). Virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM (P<0.0001) up to week 96. Emergence of resistance to ETV was not detected. The incidence of serious adverse events was low and unrelated to the study medications. CONCLUSIONS: Long-term ETV treatment was superior to LAM, with a significantly higher proportion of patients achieving VR. Both treatments were well tolerated.


Subject(s)
Antiviral Agents/therapeutic use , Guanine/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Lamivudine/therapeutic use , Adolescent , Adult , Alanine Transaminase/blood , DNA, Viral/blood , Double-Blind Method , Drug Administration Schedule , Female , Guanine/therapeutic use , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B virus/isolation & purification , Humans , Male , Middle Aged , Republic of Korea , Sustained Virologic Response , Treatment Outcome , Young Adult
3.
Korean J Gastroenterol ; 64(1): 49-53, 2014 Jul.
Article in Korean | MEDLINE | ID: mdl-25073672

ABSTRACT

Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor that is usually found in women. Diagnosis of FNH mainly depends on imaging studies such as color Doppler flow imaging, computed tomography, and magnetic resonance imaging. It is characterized by the presence of stellate central scar and is nowadays incidentally diagnosed with increasing frequency due to advances in radiologic imaging technique. FNH typically presents as a single lesion in 70% of cases and generally does not progress to malignancy or recur after resection. Herein, we report a case of a young male patient with recurrent multiple FNH who underwent surgical resection for presumed hepatic adenoma on computed tomography.


Subject(s)
Focal Nodular Hyperplasia/diagnosis , Liver Neoplasms/diagnosis , Adenoma, Liver Cell/diagnosis , Adenoma, Liver Cell/pathology , Bile Ducts/pathology , Bile Ducts/surgery , Contrast Media , Focal Nodular Hyperplasia/pathology , Humans , Liver Neoplasms/pathology , Magnetic Resonance Imaging , Male , Neoplasm Recurrence, Local , Tomography, X-Ray Computed , Young Adult
5.
Antivir Ther ; 18(6): 765-73, 2013.
Article in English | MEDLINE | ID: mdl-23900457

ABSTRACT

BACKGROUND: Lamivudine resistance develops in up to 80% of patients with chronic hepatitis B (CHB) after 5 years of treatment. Cross-resistance between nucleoside/nucleotide analogues limits management options in these patients. To investigate the role of pegylated interferon-α2a as rescue therapy in these patients, the efficacy and safety of pegylated interferon-α2a between treatment-naive patients and lamivudine-resistant patients with hepatitis B e antigen (HBeAg)-positive CHB were compared. METHODS: A total of 150 HBeAg-positive CHB patients were stratified according to prior treatment. Lamivudine-resistant patients (n=64) and treatment-naive patients (n=86) received pegylated interferon-α2a once-weekly for 48 weeks and were followed-up for an additional 24 weeks. Primary end points were HBeAg loss and HBV DNA <100,000 copies/ml at end of follow-up. RESULTS: A total of 65 (76%) treatment-naive patients and 49 (77%) lamivudine-resistant patients completed treatment and 24 weeks of follow-up. Rates of HBeAg loss were comparable at end of follow-up between treatment-naive patients and lamivudine-resistant patients (20.9% and 23.4%, respectively; P=0.8423). Similarly, rates of HBV DNA<100,000 copies/ml were comparable at end of follow-up between treatment-naive patients and lamivudine-resistant patients (20.9% and 21.9%, respectively; P=1.000). There was no statistically significant difference in alanine aminotransferase normalization rates between treatment-naive patients and lamivudine-resistant patients (36.0% and 29.7%, respectively; P=0.4848). A total of one patient in each group achieved hepatitis B surface antigen (HBsAg) loss and seroconversion. The most common adverse events were those known to occur with pegylated interferon-α2a therapy, and safety profiles were similar between both patient populations. CONCLUSIONS: Pegylated interferon-α2a may be effective as a rescue therapy in patients with lamivudine-resistant HBeAg-positive CHB.


Subject(s)
Antiviral Agents/therapeutic use , Drug Resistance, Viral , Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Adult , Alanine Transaminase/blood , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Female , Follow-Up Studies , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/virology , Humans , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Lamivudine/therapeutic use , Male , Middle Aged , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Risk Factors , Treatment Outcome , Viral Load , Young Adult
6.
Clin Mol Hepatol ; 19(2): 120-30, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23837136

ABSTRACT

BACKGROUND/AIMS: The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH. METHODS: One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea. RESULTS: According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH. CONCLUSIONS: Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.


Subject(s)
Fatty Liver/pathology , Adult , Aged , Aged, 80 and over , Alanine Transaminase/blood , Asian People , Aspartate Aminotransferases/blood , Biomarkers/blood , Fatty Liver/classification , Fatty Liver/metabolism , Female , Ferritins/blood , Fibrosis/complications , Humans , Keratin-18/analysis , Male , Middle Aged , Non-alcoholic Fatty Liver Disease , Predictive Value of Tests , Prospective Studies , Republic of Korea , Severity of Illness Index , Young Adult
7.
Cytotherapy ; 15(12): 1571-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23849977

ABSTRACT

BACKGROUND AIMS: Many rodent experiments and human studies on stem cell therapy have shown promising therapeutic approaches to liver diseases. We investigated the clinical outcomes of five patients with liver failure of various causes who received autologous CD34-depleted bone marrow-derived mononuclear cell (BM-MNC) transplantation, including mesenchymal stromal cells, through the hepatic artery. METHODS: CD34-depleted BM-MNCs were obtained from five patients waiting for liver transplantation by bone marrow aspiration and using the CliniMACS CD34 Reagent System (Miltenyi Biotech, Bergisch Gladbach, Germany), and autologous hepatic artery infusion was performed. The causes of hepatic decompensation were hepatitis B virus (HBV), hepatitis C virus (HCV), propylthiouracil-induced toxic hepatitis and Wilson disease. RESULTS: Serum albumin levels improved 1 week after transplantation from 2.8 g/dL, 2.4 g/dL, 2.7 g/dL and 1.9 g/dL to 3.3 g/dL, 3.1 g/dL, 2.8 g/dL and 2.6 g/dL. Transient liver elastography data showed some change from 65 kPa, 33 kPa, 34.8 kPa and undetectable to 46.4 kPa, 19.8 kPa, 29.1 kPa and 67.8 kPa at 4 weeks after transplantation in a patient with Wilson disease, a patient with HCV, and two patients with HBV. Ascites decreased in two patients. One of the patients with HBV underwent liver transplantation 4 months after the infusion, and the hepatic progenitor markers (cytokeratin [CD]-7, CD-8, CD-9, CD-18, CD-19, c-Kit and epithelial cell adhesion molecule [EpCAM]) were highly expressed in the explanted liver. CONCLUSIONS: Serum albumin levels, liver stiffness, liver volume, subjective healthiness and quality of life improved in the study patients. Although these findings were observed in a small population, the results may suggest a promising future for autologous CD34-depleted BM-MNC transplantation as a bridge to liver transplantation in patients with liver failure.


Subject(s)
Bone Marrow Transplantation/methods , Leukocytes, Mononuclear/transplantation , Liver Cirrhosis/therapy , Liver Failure/therapy , Mesenchymal Stem Cells/cytology , Adult , Bone Marrow Transplantation/adverse effects , Female , Hepatic Artery/cytology , Hepatic Artery/surgery , Humans , Leukocytes, Mononuclear/cytology , Liver Cirrhosis/pathology , Liver Failure/pathology , Liver Failure/surgery , Male , Middle Aged , Pilot Projects , Transplantation, Autologous , Treatment Outcome
8.
J Clin Virol ; 56(4): 299-305, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23273664

ABSTRACT

BACKGROUND: Women who are taking antiviral agents and become pregnant have several options that include, continuing therapy, ceasing drugs, or switching to safer drugs. However, there are limited data on the outcome in pregnant women after withdrawal of antiviral agents. OBJECTIVES: We aimed to investigate the outcome of stopping antiviral agents in pregnant women with chronic hepatitis B virus (HBV) infection. STUDY DESIGN: In this single-center, retrospective cohort study, 12 pregnant patients who had received antiviral therapy for HBV and cease drugs after awareness of pregnancy between 2003 and 2010 were enrolled. We retrospectively studied virologic and biochemical flares during pregnancy and postpartum period. RESULTS: Median age at pregnancy was 30.5 (range, 24-35) years, median duration of antiviral drug before pregnancy was 15.3 (range, 3.0-131.3) months, and median HBV DNA at withdrawal of therapy was 4.8 (range, 1.7-8.0) log(10) copies/mL. Eight out of twelve patients (66.7%) had a viral rebound after stopping antiviral drugs during pregnancy. Severe hepatitis flares, defined as a 5-fold increase in serum alanine aminotransferase (ALT), were observed in six patients (50%) during pregnancy. However, all of these patients spontaneously recovered without an event of hepatic decompensation. High pretreatment ALT was associated with severe hepatitis flares after cessation of therapy during pregnancy. Five patients with at least 1-year treatment before pregnancy maintained low hepatitis activity after delivery. CONCLUSIONS: Pregnant women with high pretreatment ALT or those treated less than 1 year before pregnancy have high risk of severe hepatitis flares after cessation of antiviral agents.


Subject(s)
Antiviral Agents/pharmacology , Hepatitis B, Chronic/drug therapy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/virology , Adult , Alanine Transaminase/blood , Biomarkers/blood , DNA, Viral/blood , Female , Follow-Up Studies , Hepatitis B virus , Hepatitis B, Chronic/pathology , Humans , Lamivudine/pharmacology , Postpartum Period , Pregnancy , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Viral Load , Young Adult
9.
Korean J Gastroenterol ; 61(1): 46-9, 2013 Jan 25.
Article in Korean | MEDLINE | ID: mdl-23354350

ABSTRACT

Massive bleeding hemobilia occurs rarely in patients with hepatocellular carcinoma (HCC) without any invasive procedure. Upper gastrointestinal bleeding in patient with cirrhosis and abdominal pain with progressive jaundice in patient with HCC were usually thought as variceal bleeding and HCC progression respectively. We experienced recently massive bleeding hemobilia in patient with HCC who was a 73-year old man and showed sudden abdominal pain, jaundice and hematochezia. He had alcoholic cirrhosis and history of variceal bleeding. One year ago, he was diagnosed as HCC and treated with transarterial chemoembolization periodically. Sudden right upper abdominal pain occurred then subsided with onset of hemotochezia. Computed tomography showed bile duct thrombosis spreading in the intrahepatic and extrahepatic ducts, while an ampulla of vater bleeding was observed during duodenoscopy. Hemobilia could be one of the causes of massive bleeding in patients with cirrhosis and HCC especially when they had sudden abdominal pain and abrupt elevation of bilirubin.


Subject(s)
Carcinoma, Hepatocellular/diagnosis , Hemobilia/etiology , Liver Neoplasms/diagnosis , Aged , Bile Ducts, Extrahepatic , Bile Ducts, Intrahepatic , Bilirubin/analysis , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/therapy , Duodenoscopy , Embolization, Therapeutic , Humans , Jaundice/etiology , Liver Cirrhosis/complications , Liver Neoplasms/complications , Liver Neoplasms/therapy , Male , Severity of Illness Index , Thrombosis/diagnosis , Tomography, X-Ray Computed
10.
Clin Gastroenterol Hepatol ; 10(3): 291-6, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22019793

ABSTRACT

BACKGROUND & AIMS: We evaluated changes in health-related quality of life (HRQoL) in a longitudinal study of patients given antiviral therapy for chronic hepatitis B (CHB). METHODS: We analyzed changes in HRQoL reported by 2856 Korean patients with CHB who started first-line or rescue antiviral therapy from January 2007 to June 2007; the mean age of the study subjects was 43.3 years, 72% were male, 80% were positive for hepatitis B e antigen, 20% had cirrhosis, and 13% had concomitant disease. These subjects all completed the translated version of the Chronic Liver Disease Questionnaire (CLDQ) and the EuroQol-5 Dimension (EQ5D) when the study began (baseline), and at the end of a 24-week follow-up period. We analyzed changes in utility scores from baseline to 24 weeks of antiviral treatment. RESULTS: After 24 weeks of antiviral therapy, patients had significant improvements in liver function and reduced mean levels of hepatitis B virus DNA (from 6.3 to 3.9 log(10) copies/mL). Utility scores from the visual analogue scale and EQ5D improved after 24 weeks of antiviral therapy (from 0.84 ± 0.19 to 0.94 ± 0.14; P < .0001). Improved CLDQ scores were associated with virologic response (level of hepatitis B virus DNA, <4 log(10) copies/mL); scores increased from 5.21 ± 0.99 at baseline to 6.09 ± 0.72 after 24 weeks of antiviral therapy in responders, but from 5.31 ± 0.94 at baseline to 6.06 ± 0.66 in nonresponders (P = .003). CONCLUSIONS: Patients with CHB who have a virologic response to 24 weeks of antiviral therapy also have significant improvements in HRQoL, measured by EQ5D and CLDQ.


Subject(s)
Antiviral Agents/therapeutic use , DNA, Viral/blood , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/drug therapy , Viral Load , Adult , Female , Humans , Longitudinal Studies , Male , Middle Aged , Quality of Life , Republic of Korea , Statistics as Topic , Surveys and Questionnaires , Treatment Outcome
11.
Pancreas ; 40(7): 1080-6, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21926543

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate safety and efficacy of high-intensity focused ultrasound (HIFU) for advanced pancreatic cancer (PC). METHODS: Patients with PC TNM stage III or IV were included. Magnetic resonance imaging was performed 2 weeks before and after the HIFU. The ablating tumor volume was calculated by ratio of the nonperfused necrotic area of the planned area on contrast-enhanced T1-weighted image on post-HIFU magnetic resonance imaging. The ablation results were stratified into 4 ranges: 100% to 90% unenhanced area of targeting area, 90% to 50%, within 50%, and no change. RESULTS: High-intensity focused ultrasound treatment was performed without severe adverse event in 46 patients, 49 times (male-female = 25:21; mean age, 60.7 ± 10.0; TNM stage 3-stage 4 = 18:28). Average size of the PC lesion was 4.2 ± 1.4 cm (1.6-9.3 cm). After HIFU treatment, ablating tumor volume was as follows: 90% to 100% in 38 lesions, 90% to 50% in 8, and within 50% in 3. Overall median survival (S1) from initial PC diagnosis was 12.4 months. Overall survival (S2) rates at 6, 12, and 18 months from HIFU were 52.2%, 30.4%, and 21.79%, respectively, with a median survival of 7.0 months CONCLUSIONS: High-intensity focused ultrasound is safe and effective, which induced excellent local tumor control in most patients with advanced PC.


Subject(s)
High-Intensity Focused Ultrasound Ablation , Pancreatic Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Female , High-Intensity Focused Ultrasound Ablation/adverse effects , High-Intensity Focused Ultrasound Ablation/mortality , Humans , Kaplan-Meier Estimate , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Prospective Studies , Republic of Korea , Survival Rate , Time Factors , Treatment Outcome
12.
Korean J Hepatol ; 17(1): 44-50, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21494077

ABSTRACT

BACKGROUND/AIMS: Recent outbreak of hepatitis A in Korea is clearly related to the epidemiological shift of hepatitis A virus (HAV). However, nationwide seroprevalence data have been limited. This study estimated the nationwide, age- and area-adjusted anti-HAV prevalence from 2005 to 2009. METHODS: Retrospective analysis of the results of total anti-HAV test in 25,140 cases which were requested by 1,699 medical institutions throughout the nation to Seoul Clinical Laboratory from Jan. 1 2005 to Dec. 31 2009 was performed. The estimated seroprevalence was adjusted by area and age of the standard population based on the 2005 Census data from Korea National Statistical Office. RESULTS: The area-adjusted anti-HAV prevalence in the children younger than 10 years were 33.4% in 2005 and 69.9% in 2009. The most susceptible age groups to HAV infection during the last 5 years were teenagers and the young adults in their age of twenties. The area-adjusted seroprevalence in 2009 were 11.9% in the age group of 20-29 years, 23.4% in the age group of 10-19 years, 48.4% in the age group of 30-39 years. The population in 40-49 years showed geographically different seroprevalence with the lowest rate in Seoul (80%). CONCLUSIONS: The most susceptible age group to HAV infection is 10-29 years, while the young children less than 10 years showed about 70% seropositivity. The changing seroepidemiology should be monitored continuously for the proper vaccination and patient care.


Subject(s)
Hepatitis A Antibodies/blood , Hepatitis A/epidemiology , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Female , Hepatitis A Virus, Human/immunology , Humans , Infant , Infant, Newborn , Male , Middle Aged , Retrospective Studies , Seroepidemiologic Studies
13.
J Pharm Pharmacol ; 63(5): 627-35, 2011 May.
Article in English | MEDLINE | ID: mdl-21492164

ABSTRACT

OBJECTIVES: Oltipraz, a cancer chemopreventive agent, has an anticirrhotic effect in animals. A phase II trial was designed to investigate the preliminary efficacy of oltipraz therapy in liver fibrosis or cirrhosis. METHOD: Of 83 patients who were randomized to receive placebo, oltipraz 60 mg bid or oltipraz 90 mg qd for 24 weeks, 68 completed the study without any major protocol violation. Pre- and post-treatment liver biopsies, and blood fibrosis markers were assessed. KEY FINDINGS: Twenty-four weeks of oltipraz treatment showed no significant differences in the proportions of patients showing an improvement in histological outcomes, including Ishak fibrosis score. In the oltipraz 60 mg bid group, there was a trend of decreases in hepatic collagen area and plasma transforming growth factor-ß1 (TGF-ß1, a blood fibrosis marker) levels from baseline to week 24. In the per-protocol population (n = 68), decreases in plasma TGF-ß1 correlated with those in the Ishak fibrosis score, suggesting that circulating TGF-ß1 serves a possible indicator for fibrosis treatment. CONCLUSIONS: No significant differences in liver histological outcomes were seen among the three treatment groups in this 24-week pilot study. Our finding indicates an association between TGF-ß1 repression and improvement in the histological index of fibrosis.


Subject(s)
Anticarcinogenic Agents/therapeutic use , Collagen/metabolism , Liver Cirrhosis/drug therapy , Liver/drug effects , Pyrazines/therapeutic use , Transforming Growth Factor beta1/blood , Adult , Anticarcinogenic Agents/pharmacology , Biomarkers/blood , Biopsy , Double-Blind Method , Female , Hepatitis B/complications , Hepatitis C/complications , Humans , Liver/metabolism , Liver/pathology , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Male , Middle Aged , Pyrazines/pharmacology , Thiones , Thiophenes
14.
Hepatology ; 52(6): 2053-64, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20890948

ABSTRACT

UNLABELLED: Cadherins mediate cell-cell adhesion and catenin (ctn)-related signaling pathways. Liver fibrosis is accompanied by the loss of E-cadherin (ECAD), which promotes the process of epithelial-mesenchymal transition. Currently, no information is available about the inhibitory role of ECAD in hepatic stellate cell activation. Because of ECAD's potential for inhibiting the induction of transforming growth factor ß1 (TGFß1), we investigated whether ECAD overexpression prevents TGFß1 gene induction; we also examined what the molecular basis could be. Forced expression of ECAD decreased α-smooth muscle actin and vimentin levels and caused decreases in the constitutive and inducible expression of the TGFß1 gene and its downstream genes. ECAD overexpression decreased Smad3 phosphorylation, weakly decreased Smad2 phosphorylation, and thus inhibited Smad reporter activity induced by either treatment with TGFß1 or Smad3 overexpression. Overexpression of a dominant negative mutant of ras homolog gene family A (RhoA) diminished the ability of TGFß1 to elicit its own gene induction. Consistently, transfection with a constitutively active mutant of RhoA reversed the inhibition of TGFß1-inducible or Smad3-inducible reporter activity by ECAD. Studies using the mutant constructs of ECAD revealed that the p120-ctn binding domain of ECAD was responsible for TGFß1 repression. Consistently, ECAD was capable of binding p120-ctn, which recruited RhoA; this prevented TGFß1 from increasing RhoA-mediated Smad3 phosphorylation. In the liver samples of patients with mild or severe fibrosis, ECAD expression reciprocally correlated with the severity of fibrosis. CONCLUSION: Our results demonstrate that ECAD inhibits Smad3/2 phosphorylation by recruiting RhoA to p120-ctn at the p120-ctn binding domain, whereas the loss of ECAD due to cadherin switching promotes the up-regulation of TGFß1 and its target genes, and facilitates liver fibrosis.


Subject(s)
Cadherins/physiology , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/physiology , Liver Cirrhosis/physiopathology , Smad3 Protein/metabolism , Transforming Growth Factor beta1/antagonists & inhibitors , Actins/biosynthesis , Animals , Dimethylnitrosamine , Epithelial-Mesenchymal Transition , Female , Humans , Liver Cirrhosis/chemically induced , Male , Mice , Phosphorylation , Rats , Smad2 Protein , rhoA GTP-Binding Protein/antagonists & inhibitors , rhoA GTP-Binding Protein/metabolism
15.
Korean J Hepatol ; 16(1): 19-28, 2010 Mar.
Article in Korean | MEDLINE | ID: mdl-20375639

ABSTRACT

BACKGROUND/AIMS: According to recent prevalence of hepatitis A virus (HAV) infection, acute liver failure (ALF) due to HAV infection is observed frequently in parallel. The aim of this study was to elucidate the clinical, laboratory, and pathologic features of patients who have undergone emergency liver transplantation (LT) due to fulminant HAV infection. METHODS: Clinical, laboratory, and pathologic data of 11 transplant recipients with anti-HAV IgM-positive ALF between December 2007 and May 2009 were analyzed, and compared with data of 10 recipients who underwent LT for the management of ALF due to other causes. RESULTS: The median age of the patients with HAV-related ALF was 34 years (range: 15-43 years). The levels of hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine were higher and the level of bilirubin was lower in the HAV-related ALF group than in the other group (P=0.005, 0.001, 0.001, 0.010, and 0.003, respectively). The time from the onset of initial symptoms to the development of encephalopathy was shorter in the HAV-related ALF group than in the other group (median 5 days, range: 4-13 days; P<0.001). In patients with HAV-related ALF, laboratory findings and clinical prognostic parameters including the Acute Liver Failure Study Group prognostic index, King's College criteria, and model for endstage liver disease (MELD) and Child-Pugh scores were not associated with the grade of hepatic encephalopathy or time of progression to encephalopathy. CONCLUSIONS: The results of this study indicate that the clinical condition of patients with HAV-related ALF requiring emergency LT aggravates rapidly. Prognostic parameters are not sufficient for discriminating transplant candidates in patients with fulminant hepatitis A.


Subject(s)
Hepatitis A/complications , Liver Failure, Acute/diagnosis , Liver Transplantation , Adolescent , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Bilirubin/blood , Creatine/blood , Emergencies , Female , Hemoglobins/analysis , Hepatitis A Antibodies/immunology , Hepatitis A Antibodies/metabolism , Humans , Immunoglobulin M/metabolism , Liver Failure, Acute/complications , Liver Failure, Acute/therapy , Male , Middle Aged , Prognosis , Severity of Illness Index , Time Factors
16.
Antimicrob Agents Chemother ; 54(3): 1242-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20028815

ABSTRACT

We characterized the early viral kinetic profiles of telbivudine and entecavir and the effects of these potent nucleoside analogs on hepatitis B virus (HBV) DNA and alanine aminotransferase levels in adults with hepatitis B e antigen-positive compensated chronic hepatitis B. Forty-four patients were enrolled in this open-label, parallel-group, multicenter study and randomized to receive telbivudine or entecavir for 12 weeks. Reductions in hepatitis B virus DNA and alanine aminotransferase levels from baseline to weeks 2, 4, 8, and 12 were assessed. Viral kinetic parameters, including viral clearance per day, loss of infected cells per day, and efficiency of inhibition of viral production, were estimated by using a biphasic mathematical model. Statistical analyses were limited to descriptive analyses. The 2 treatment groups achieved similar reductions in HBV DNA and alanine aminotransferase levels. Mean reductions in levels of hepatitis B virus DNA at week 12 were 6.6 +/- 1.6 and 6.5 +/- 1.5 log(10) copies/ml for the telbivudine- and entecavir-treated patients, respectively. There were no significant differences between groups in values for mean viral clearance per day, mean loss of infected cells per day, or efficiency of blocking viral production. The safety profiles for both medications were favorable. During the first 12 weeks of treatment, telbivudine and entecavir demonstrated similar antiviral potencies, resulting in a rapid and profound suppression of serum hepatitis B virus DNA and reduction of alanine aminotransferase levels. No differences in the effects of these 2 agents on early viral kinetics were observed. Both medications were well tolerated.


Subject(s)
Antiviral Agents/pharmacology , Guanine/analogs & derivatives , Hepatitis B e Antigens/blood , Hepatitis B virus/drug effects , Hepatitis B, Chronic/drug therapy , Nucleosides/pharmacology , Pyrimidinones/pharmacology , Adult , Alanine Transaminase/blood , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , DNA, Viral/blood , Female , Guanine/administration & dosage , Guanine/pharmacology , Guanine/therapeutic use , Hepatitis B, Chronic/virology , Humans , Kinetics , Male , Middle Aged , Nucleosides/administration & dosage , Nucleosides/therapeutic use , Pyrimidinones/administration & dosage , Pyrimidinones/therapeutic use , Telbivudine , Thymidine/analogs & derivatives , Treatment Outcome
17.
Clin Gastroenterol Hepatol ; 8(1): 60-5, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19804841

ABSTRACT

BACKGROUND & AIMS: Little is known about whether histologic data can predict which patients with hepatitis B virus (HBV)-related decompensated cirrhosis will respond to antiviral therapies. We assessed the relationship between serum HBV DNA load and histologic activity by analyzing liver specimens from patients with decompensated cirrhosis. METHODS: The study included 72 consecutive patients who underwent liver transplantation for HBV-related decompensated cirrhosis between November 2000 and March 2008. None of the patients had received nucleoside or nucleotide analogues more than 2 weeks before transplantation. Serum HBV DNA levels at the time of transplantation were compared with histologic activity in explanted liver specimens. RESULTS: The median HBV DNA level of the 72 patients was 5.40 log(10) copies/mL (range, 1.45-8.00 log(10) copies/mL). There were no differences in HBV DNA level between patients grouped according to lobular or portoperiportal activity (P = .678, P = .291, respectively). Of 16 patients (22.2%) with HBV DNA levels less than 2000 copies/mL, 8 patients (50.0%) had moderate or severe portoperiportal activity; their median alanine aminotransferase level was 30.5 U/L (range, 12-135 U/L). CONCLUSIONS: HBV DNA load does not reflect histologic activity in patients with HBV-related decompensated cirrhosis. Although patients with decompensated cirrhosis might have normal levels of alanine aminotransferase and a low level of viremia (<2000 copies/mL), they still can have significant portoperiportal activity.


Subject(s)
Hepatitis B virus/isolation & purification , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Liver Cirrhosis/pathology , Serum/virology , Severity of Illness Index , Viral Load , Adult , DNA, Viral/blood , Female , Histocytochemistry , Humans , Male , Middle Aged , Prospective Studies , Statistics as Topic
18.
Korean J Hepatol ; 15(2): 131-9, 2009 Jun.
Article in Korean | MEDLINE | ID: mdl-19581765

ABSTRACT

BACKGROUND/AIMS: This study examined the effects of hepatitis B virus (HBV) infection state and immunologic capability in both the recipients and donors of allogenic hematopoietic stem-cell transplantation (allo-HSCT) on changes in HBV serologic markers in recipients. METHODS: A total of 537 patients underwent allo-HSCT for the treatment of leukemia, malignant lymphoma, and solid tumor. HBV serologic markers were examined in both recipients and donors prior to and following the transplantation. The mean follow-up period was 36.6 months (range 3-80 months). RESULTS: Of the 537 patients who underwent allo-HSCT, 45 recipients were positive for HBsAg prior to transplantation. Of these 45 patients, 21 were transplanted from anti-HBs-positive donors and the remaining 24 were transplanted from anti-HBs-negative donors. In the former cases, seroconversion was noted in 4 of the 21 patients (19%). In the latter cases, however, no seroconversion was noted following the transplantation. Thirty patients who were negative for both HBsAg and anti-HBs were transplanted from anti-HBs-positive donors, and 15 out of 30 patients (50%) acquired anti-HBs. Four hundred and seven patients who were positive for anti-HBs were transplanted from anti-HBs-positive or HbsAg-negative donors; 8 of these proved HBsAg-positive following the transplantation. There were no changes in HBV serological markers following transplantation in 41 patients who were transplanted from HbsAg-positive donors. CONCLUSIONS: Due to the adoptive immunity that was transferred from anti-HBs-positive donors, a seroconversion of HBsAg could occur in some HBsAg-positive recipients. HBsAg-positive donors had a lesser effect on the HBV serologic markers of recipients. However, a reactivation of HBV can occur following hematopoietic stem-cell transplantation in the cases of recipients or donors with a history of HBV, infection by an accompanying immune suppression. Therefore, prevention should be instigated.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hepatitis B/immunology , Adolescent , Adult , Aged , Biomarkers/blood , Female , Hepatitis B/diagnosis , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Humans , Male , Middle Aged , Retrospective Studies , Tissue Donors , Transplantation, Homologous , Virus Activation
19.
Korean J Hepatol ; 15(1): 85-9, 2009 Mar.
Article in Korean | MEDLINE | ID: mdl-19346789

ABSTRACT

A 29-year-old man was admitted to hospital with fever, myalgia, and sore throat. Initial laboratory findings were compatible with acute hepatitis; he was positive for the serologic marker for acute hepatitis A. On the 3rd day of admission, in spite of normalization of body temperature and a reduction in serum liver enzyme levels, serum levels of creatinine phosphokinase had increased up to 16,949 U/L. The patient recovered with supportive therapy and was discharged on the 12th day. We report a case of acute hepatitis A complicated by rhabdomyolysis during hospitalization.


Subject(s)
Hepatitis A/diagnosis , Rhabdomyolysis/diagnosis , Acute Disease , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Creatine Kinase/blood , Hepatitis A/complications , Hospitalization , Humans , Male , Rhabdomyolysis/etiology
20.
Eur J Gastroenterol Hepatol ; 20(7): 707-9, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18679076

ABSTRACT

Different therapeutic strategies have been tried when liver metastasis develops after a gastrectomy for gastric cancer, but the disease still has a poor prognosis. We present a 35-year-old woman who achieved complete radiological remission of liver metastases from advanced gastric cancer after a single therapeutic high intensity focused ultrasound session. Our observations suggest that high intensity focused ultrasound combined with chemotherapy may be an additional treatment option for patients with liver metastases from advanced gastric cancer.


Subject(s)
Carcinoma, Signet Ring Cell/secondary , Liver Neoplasms/secondary , Stomach Neoplasms/surgery , Ultrasonic Therapy/methods , Adult , Carcinoma, Signet Ring Cell/diagnosis , Carcinoma, Signet Ring Cell/therapy , Female , Follow-Up Studies , Gastrectomy , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/therapy , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Treatment Outcome
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